Pain is prevalent. It is estimated that more than 50 million Americans live with chronic pain caused by various diseases or disorders, and each year nearly 25 million people suffer with acute pain as a result of injury or surgery. Furthermore, chronic pain has been said to be the most costly health problem in America. Estimated annual costs, including direct medical expenses, lost income, lost productivity, compensation payments, and legal charges are currently about $90 billion. And the numbers are rising. Estimates indicate that by 2030, 148 million people will have chronic conditions, and associated annual direct costs will rise to $798 billion. Thus, pain management has been identified as one of the most difficult challenges for the health care industry.
Non-steroidal anti-inflammatory drug NSAIDs (also referred to as non-narcotic analgesics) are administered for the treatment of mild to severe pain and in some instances are prescribed for continuous use in the treatment of acute or chronic inflammatory states such as rheumatoid arthritis and osteoarthritis. NSAIDs are well absorbed following oral administration but there is a high potential for adverse side-effects such as ulcerations, abdominal pain, cramping, nausea, gastritis, kidney disease, angiodema, pancreatitis, and even serious gastrointestinal bleeding and liver toxicity at the upper limits of their effective dose ranges. Thus, the ability to use higher dosages of NSAIDs is generally limited. Moreover, above each NSAIDs' upper limit or ceiling, administration of additional NSAID or use of combinations of NSAIDs does not usually increase the analgesic or anti-inflammatory effect.
Opioid analgesics (also referred to as narcotic analgesics) such as buprenorphine are often used when pain control with NSAIDs is ineffective. While narcotic analgesics vary considerably in their chemical structures and pharmacological properties, almost all suffer the disadvantages of tolerance and possible addiction with continued usage.
Narcotic analgesics are classified generally as narcotic agonists or narcotic antagonists. Drugs that activate receptors in the brain are termed agonists. Hence, a drug that activates an opioid receptor is termed an opioid agonist. The repeated administration of opioid agonists results in dose-dependent physical dependence and tolerance. Physical dependence manifests as a characteristic set of withdrawal signs and symptoms upon reduction, cessation, or loss of an active compound at an opioid receptor. These withdrawal signs and symptoms can include sweating, cramps, aches, lacrimation, diarrhea, rhinorrhea, piloerection, and pupillary dilation. A drug that binds to a receptor in the brain to block the receptor rather than activate it is termed an antagonist. Examples of opioid antagonists are naltrexone and naloxone. Partial agonists are drugs that activate receptors in the brain but not to the extent as full agonists. Buprenorphine is an example of a partial agonist (also referred to as a partial opioid agonist or opioid analgesic). It is the partial agonist properties of buprenorphine that contribute to its effectiveness in pain management and provide the added benefit of reduced dependence on and/or addiction to opioids. Consistent with its agonist action at opioid receptors, however, partial agonists such as buprenorphine are still abusable, particularly by individuals who are not already physically dependents on opioids.
Although NSAIDs and opioid analgesics are individually limited in their ability to effectively manage pain without inducing adverse side effects such as gastrointestinal disorders, dependence and/or addiction to, and withdrawal upon cessation or reduction, it has now been found that a pharmaceutical composition for sublingual administration having relatively low effective amounts of a NSAID such as piroxicam in combination with relatively high effective amounts of an opioid analgesic such as buprenorphine improves upon existing pain medications and provides the additional benefit of reduced side effects.